Companion animals

Genome-wide association study suggests PPP3CA as a candidate gene for canine atopic dermatitis

---

Abstract

Canine atopic dermatitis (cAD) is a common, chronic inflammatory skin disease that closely mirrors human atopic dermatitis in clinical presentation and immunopathology. It is characterized by pruritus (itchiness), erythema (redness), and compromised skin barrier integrity. cAD is a multifactorial condition influenced by genetic predisposition, immune dysregulation, and environmental exposures. Affected dogs often exhibit elevated serum IgE and T cell-mediated hypersensitivity to environmental allergens. The disease shows strong breed predisposition, with specific genetic loci identified in breeds such as West Highland White Terriers, Labrador Retrievers, and German Shepherds. However, the mechanisms by which these genetic variants contribute to immune imbalance or skin dysfunction remain poorly understood. Moreover, most previous studies have been limited to single-breed or low-diversity cohorts, constraining the generalizability of findings. Our objective is to perform a genome-wide association study (GWAS) in a genetically diverse canine cohort to identify loci associated with atopic dermatitis with potential cross-breed relevance. Our research leverages data from the Dog Aging Project (DAP). DAP is a nationwide longitudinal study collecting health, environmental, and genetic data from tens of thousands of companion dogs. The DAP has genotyped >7500 of these dogs from diverse breeds and mixed ancestry. We identified 200 dogs as cases based on owner-reported cAD with available genotyping. As controls, we selected 1594 dogs aged 8 years or older with no history of skin disease, minimizing the chance of late-onset or subclinical cases. To reduce confounding due to breed predisposition, the breed distribution of the 200 cAD cases was first quantified, and control dogs were subsampled to be similar to this distribution. Genotype data from CanFam3.1 SNPs were processed in PLINK, and analyses were performed using only high-frequency SNPs (MAF >0.01). After quality control, 3,304,406 SNPs were retained for analysis. A GWAS was conducted using the Gaston package in R, which applies a linear mixed model to account for population structure and kinship. Our analysis revealed an association that approached significance between cAD and a locus on chromosome 32 near the gene PPP3CA (P =9.98E-07), which encodes the catalytic subunit of calcineurin, a key regulator of T-cell activation. This finding suggests a potential immunogenetic mechanism underlying cAD, providing a promising entry point for exploring the molecular pathways linking genetic variation to immune dysfunction in cAD. Prior evidence has linked PPP3CA to immune dysregulation and chronic inflammation. PPP3CA has also been implicated in mastitis in cattle and litter size in pigs and sheep, suggesting its functional importance across multiple species. In conclusion, our genome-wide analysis reveals a moderate association between PPP3CA and cAD, suggesting this gene may have a role in immune-mediated disease and highlighting its potential as a cross-species candidate gene.

Keywords: 2026

How to Cite:

Wu, Z. & Baker, L., (2026) “Genome-wide association study suggests PPP3CA as a candidate gene for canine atopic dermatitis”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2285543. doi: https://doi.org/10.31274/wcgalp.23736

Rights: 1